Hepatitis: San Francisco

Anonymous00392, Yee HS, Currie SL, Darling JM, Wright TL. · Department of Veterans Affairs Hepatitis C Resource Center Program, San Francisco, California, USA. · Am J Gastroenterol. · Pubmed #17032203 No free full text.

Abstract: Chronic hepatitis C virus (HCV) infection affects approximately 1.3% of the general U.S. population and 5-10% of veterans who use Department of Veterans Affairs medical services. Chronic HCV is clearly linked to the development of cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease requiring liver transplantation. The consequences of HCV infection constitute a significant disease burden and demonstrate the need for effective medical care. Treatment of chronic HCV is aimed at slowing disease progression, preventing complications of cirrhosis, reducing the risk of HCC, and treating extrahepatic complications of the virus. As part of a comprehensive approach to HCV management, antiviral therapy with peginterferon alfa combined with ribavirin is the current standard of care. Antiviral therapy should be provided to those individuals who meet criteria for treatment and who are at greatest risk for progressive liver disease. Many of these patients may have comorbid medical and psychiatric conditions, which may worsen while on antiviral therapy. Current antiviral regimens are associated with significant adverse effects that can lead to noncompliance, dose reduction, and treatment discontinuation. To overcome these barriers and to address these issues, it has become crucial to facilitate a multidisciplinary team who can respond to and provide HCV-specific care and treatment. Screening for HCV, preventing transmission, delaying disease progression, ensuring appropriate antiviral therapy, and managing treatment-related adverse effects can improve patient quality of life, treatment adherence, and ultimately, improve patient outcomes.

Tien PC, Anonymous00369, Anonymous00370. · VAMC Infectious Disease Section, San Francisco, CA 94121, USA. · Am J Gastroenterol. · Pubmed #16181388 No free full text.

Abstract: Nearly 40% of human immunodeficiency virus- (HIV-) infected veterans on highly active antiretroviral therapy (HAART) in the United States are coinfected with hepatitis C virus (HCV). With the increased survival due to declining opportunistic infections as a result of HAART, HCV-associated liver disease has become a leading cause of death in HIV-infected individuals. HCV infection has been shown to lead to rapid progression of HCV-related liver disease in HIV infection. Results from recent clinical trials in HIV/HCV-coinfected patients show improved response rates using pegylated formulations of interferon plus ribavirin when compared to standard interferon plus ribavirin. However, the treatment of HCV in HIV/HCV-coinfected patients can be complicated by the hepatotoxic and myelosuppressive effects of HIV therapy and HIV infection itself. Prior to initiating HCV therapy, HIV therapy should be optimized by improving immune suppression and avoiding specific antiretroviral drugs that may cause hepatotoxicity and myelosuppression. In the event of treatment-related neutropenia or anemia during HCV therapy, the use of growth factors should be considered to maximize sustained virologic response to HCV therapy. In HIV/HCV-coinfected patients with end-stage liver disease, liver transplantation is being investigated and shows promise as a potential therapeutic option. With the recent advances in the treatment of HCV in HIV/HCV-coinfected individuals, all HIV/HCV-coinfected patients eligible for HCV treatment should be evaluated for HCV combination therapy with careful consideration of their HIV disease.

Gish RG. · Liver Transplant Program, California Pacific Medical Center, 2340 Clay Street, San Francisco, CA 94115, USA. · Gastroenterol Clin North Am. · Pubmed #15081104 No free full text.

This publication has no abstract.

Ramachandran R, Kakar S. · Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA. · J Clin Pathol. · Pubmed #19474352 No free full text.

Abstract: The diagnosis of drug-induced liver injury (DILI) is a challenging problem, often confounded by incomplete clinical information and the difficulty of eliciting exposure to herbal products, over-the-counter agents and toxins. The task is further rendered difficult on biopsy, as drugs can mimic all the patterns found in primary liver disease. Acute hepatitis, with or without cholestasis, is the most common histological pattern of DILI, and drugs such as acetaminophen are the leading causes of acute liver failure. Most cases of DILI resolve on discontinuation of the drug, but recovery can take months or rarely the disease can progress despite drug withdrawal. Drugs such as methotrexate can lead to chronic hepatitis and cirrhosis, while others such as minocycline, nitrofurantoin and methyldopa are implicated in autoimmune hepatitis. Prolonged cholestasis and ductopenia resembling primary chronic biliary disease can occur. Drug-induced steatohepatitis is also an uncommon pattern, but is well described with drugs such as amiodarone and irinotecan. In the presence of risk factors such as obesity and diabetes, some drugs such as tamoxifen, oestrogens and nifedipine can precipitate or exacerbate steatohepatitis. Other observed patterns include granulomatous hepatitis, vascular injury (eg, sinusoidal obstruction syndrome), Ito cell lipidosis and neoplasms (eg, adenomas).

Houghton M. · Epiphany Biosciences Inc., San Francisco, CA 94111, USA. · Liver Int. · Pubmed #19207970 No free full text.

Abstract: After nearly 6 years of intensive investigations between 1982 and 1988 in my laboratory at Chiron corporation, in which numerous molecular biological methods were used to investigate the viral aetiology of parenterally transmitted non-A, non-B viral hepatitis (NANBH), a single cDNA clone (5-1-1) was isolated that was shown to be derived from a new flavi-like virus, termed the hepatitis C virus (HCV). After screening hundreds of millions of bacterial cDNA clones derived from different liver and plasma samples obtained from experimentally infected chimpanzees, a single HCV clone was eventually isolated using a novel, blind immunoscreening method in which antibodies derived from a clinically diagnosed NANBH patient were used to identify a cDNA clone encoding an immunodominant epitope within HCV nonstructural protein 4. Its viral origin was demonstrated by its specific hybridization to a large single-stranded RNA molecule of approximately 10,000 nucleotides found only in NANBH-infected samples that shared distant sequence identity with flaviviruses. Further, HCV clone 5-1-1 was shown to be extrachromosomal and to encode an antigen eliciting antibody seroconversion only in NANBH-infected chimpanzees and humans. Subsequent work demonstrated that HCV was the principal cause of parenterally transmitted NANBH around the world, with an estimated 170 million global carriers and that blood screening tests detecting circulating HCV antibodies and viral RNA could effectively eradicate the transmission of transfusion-associated NANBH. Key viral-encoded enzymes essential to its life cycle are now the targets of vigorous, ongoing drug development activities, and the feasibility of successful vaccination strategies has been demonstrated using the valuable chimpanzee model, without which any progress on HCV would not have been possible. My colleagues and coworkers who made essential contributions to the discovery of HCV were George Kuo, who had his own laboratory at Chiron and who provided intellectual and practical input, Dan Bradley of the Centers for Disease Control and Prevention, who provided a large supply of well-characterized chimpanzee samples and knowledge of the NANBH field, and Qui-Lim Choo, in my own laboratory, who provided many years of outstandingly dedicated and precise molecular biology expertise.

Rook M, Rosenthal P. · Pediatric Gastroenterology, Hepatology and Nutrition, University of California San Francisco, 500 Parnassus Avenue, MU4E, Box 0136, San Francisco, CA 94143, USA. · Curr Gastroenterol Rep. · Pubmed #19166664 No free full text.

Abstract: The etiology of liver disease in childhood varies significantly from its etiology in the adult population. More children with complex diseases are surviving into adulthood, providing challenges to the primary care provider. Adults with pediatric liver disease differ in management, treatment, complications, and extrahepatic considerations. To provide these patients with an optimal transition into the adult health care system, the provider needs a comprehensive knowledge of the common causes of childhood liver disease and their implications and must understand the differences in caring for these patients. This review addresses some of the most common childhood liver diseases, their causes, presentation, evaluation, management, complications, and additional concerns.

Quan DJ. · Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, CA, USA. · Nephrol Nurs J. · Pubmed #18856082 No free full text.

Abstract: Chronic infection with hepatitis B virus can lead to liver disease, cirrhosis, and hepatocellular carcinoma. Treatment options include interferons and antiviral drugs. The interferons have immunomodulatory, antiproliferative, and antiviral effects. Nucleoside analogs, such as entecavir, lamivudine and telbivudine, and neucleotide analogs, such as adefovir and tenofovir, exhibit antiviral effects by inhibiting viral replication. Treatment is directed at suppressing viral replication and halting the progression of disease.

Terrault NA. · Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco, CA 94143, USA. · Liver Transpl. · Pubmed #18825697 No free full text.

Abstract: 1. Pretransplant therapy, using a low-accelerating-dose regimen, is an option for patients with mildly decompensated liver disease and low laboratory Model for End-Stage Liver Disease scores. Achievement of an on-treatment virologic response is the goal of therapy. Preliminary data suggest that up to two-thirds of patients who become hepatitis C virus RNA-negative on treatment will be hepatitis C virus infection-free post-transplantation. 2. Effective prophylactic therapies are not available. Hepatitis C antibody therapy has been ineffective in preventing hepatitis C virus infection in studies to date. 3. Preemptive antiviral therapy started within weeks of transplantation is limited by tolerability, particularly in patients with high Model for End-Stage Liver Disease scores pre-transplantation. Rates of sustained virologic response vary from 8% to 39%. Histological benefits in virologic nonresponders have been demonstrated. 4. Posttransplant antiviral therapy in those with evidence of recurrent disease is the mainstay of management. A combination of pegylated interferon and ribavirin is the treatment of choice, and sustained virologic response is achieved with 48 weeks of treatment in approximately 30% of treated patients. Attainment of early loss of hepatitis C virus RNA is highly predictive of sustained virologic response. Histologic improvements are seen in responders. Survival is prolonged among those achieving a sustained virologic response. 5. Posttransplant antiviral therapy is limited by poor tolerability and the frequent need for dose reductions and/or discontinuation. Immunologic complications, including acute rejection, chronic rejection, and autoimmune-like hepatitis, occur in association with therapy, albeit at low rates. 6. Hepatitis C virus-infected liver transplant recipients represent an important patient population in need of new therapeutics options to prevent patient and graft losses due to recurrent hepatitis C virus disease.

Inductivo-Yu I, Bonacini M. · International Hepatology Scholar Program, California Pacific Medical Center, San Francisco, California 94115, USA. · Curr Drug Saf. · Pubmed #18690975 No free full text.

Abstract: With the advent of highly active antiretroviral therapy (HAART), the reduction in overall mortality and morbidity in HIV patients has been accompanied by the emergence of liver disease as a leading cause of death. Elevated liver enzymes may be due to HAART or to other risk factors, including hepatitis co-infection and alcohol use. The different components of HAART are each associated with different risks of liver toxicity. Most drugs are metabolized by cytochrome P450 enzymes in the liver, and this may be affected by liver disease. The mechanisms for drug-induced liver injury include dose-dependent toxicity, hypersensitivity reactions, idiosyncratic reactions, mitochondrial toxicity, and immune reconstitution. The diagnosis of drug-induced liver injury is exclusionary. Once diagnosed, management generally involves discontinuation of the offending drug(s). A number of studies in progress are investigating whether treatment of hepatitis co-infection can improve the tolerability of HAART.

Monto A, Currie S, Wright TL. · San Francisco Veterans Affairs Medical Center, CA, USA. · J Addict Dis. · Pubmed #18681191 No free full text.

Abstract: Liver disease is a major health problem for individuals with a history of injection drug use. This is mainly from the hepatitis C virus (HCV), with or without co-infection with HIV. HCV-associated liver disease takes decades to develop into cirrhosis, from which it can adversely affect health. HIV coinfection is among the factors that are often associated with liver disease progression, and efforts to understand liver disease progression in HIV-HCV coinfected patients remain important. Maintaining high CD4 counts and avoiding alcohol intake are associated with slower liver disease progression. Pegylated interferon and ribavirin combination therapy has the potential to clear HCV, which provides the strongest health benefit to patients affected by the virus, although this can be difficult to accomplish for many reasons. Steatosis, fat within the liver, may also have important pathological implications for liver disease related to HCV. Limiting liver disease progression in IDUs with hepatitis C may well be best accomplished through promoting their full utilization of health care.

Sheikh MY, Choi J, Qadri I, Friedman JE, Sanyal AJ. · Division of Gastroenterology and Hepatology, University of California San Francisco Fresno Education Program, Community Regional Medical Center, Fresno, CA 93721, USA. · Hepatology. · Pubmed #18446789 No free full text.

Abstract: Chronic infection with hepatitis C virus (HCV) can induce insulin resistance (IR) in a genotype-dependent fashion, thus contributing to steatosis, progression of fibrosis and resistance to interferon therapy. The molecular mechanisms in genotype 1 patients that lead to metabolic syndrome are still ambiguous. Based on our current understanding, HCV proteins associate with mitochondria and endoplasmic reticulum and promote oxidative stress. The latter mediates signals involving the p38 mitogen-activated protein kinase and activates nuclear factor kappa B. This transcription factor plays a key role in the expression of cytokines, tumor necrosis factor alpha (TNF-alpha), interleukin 6, interleukin 8, tumor growth factor beta, and Fas ligand. TNF-alpha inhibits the function of insulin receptor substrates and decreases the expression of the glucose transporter and lipoprotein lipase in peripheral tissues, which is responsible for the promotion of insulin resistance. Furthermore, reduced adiponectin levels, loss of adiponectin receptors, and decreased anti-inflammatory peroxisome proliferator-activated receptor alpha in the liver of HCV patients may contribute to reduced fatty acid oxidation, inflammation, and eventually lipotoxicity. This chain of events may be initiated by HCV-associated IR and provides a direction for future research in the areas of therapeutic intervention.

Rosenthal P. · University of California, San Francisco, 94143-0136, USA. · J Pediatr Gastroenterol Nutr. · Pubmed #18367947 No free full text.

Abstract: It is becoming increasingly evident that children, like adults, with chronic viral or metabolic liver diseases are at risk for the development of hepatocarcinoma. The aims of this article are to review the risk factors for hepatocarcinoma in chronic viral or metabolic liver disease, outline potential pathogenic mechanisms of hepatocarcinoma, and describe surveillance strategies, clinical evaluation, and management of hepatocarcinoma in children.

Nguyen TT, Taylor V, Chen MS, Bastani R, Maxwell AE, McPhee SJ. · Vietnamese Community Health Promotion Project and UCSF Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA. · J Cancer Educ. · Pubmed #18067441 No free full text.

Abstract: BACKGROUND: Due to the high prevalence of hepatitis B, Asian Americans have high rates of liver cancer. Screening for hepatitis B leads to monitoring and treatment and prevent further infection through vaccination of contacts. METHODS: We reviewed the published literature up to 2006 on hepatitis B awareness, knowledge, and screening among Asian Americans. RESULTS: Many Asian Americans lack knowledge about hepatitis B and have not been screened. Sociodemographics, knowledge, beliefs, and health care variables are associated with screening. CONCLUSIONS: Further research and health policy changes are needed to address the problem of hepatitis B and liver cancer among Asian Americans.

Gish RG, Locarnini S. · California Pacific Medical Center, 2340 Clay St., Room 223, San Francisco, CA 94115, USA. · Clin Liver Dis. · Pubmed #17981228 No free full text.

Abstract: The global prevalence of chronic hepatitis B and its associated serious sequelae demand technologically advanced techniques of management. Nucleic acid testing (NAT) plays a key role in the diagnosis, surveillance, and treatment of chronic hepatitis B. NAT includes quantitative PCR-based HBV DNA assays, HBV genotyping, tests for mutations associated with resistance to antiviral medications, and assays to detect precore and core promoter mutations. This article reviews the uses of NAT in the diagnosis and management of chronic hepatitis B.

Coffin CS, Terrault NA. · Department of Medicine, University of California at San Francisco, San Francisco, CA 94143, USA. · J Viral Hepat. · Pubmed #17958641 No free full text.

Abstract: Advances in hepatitis B virus (HBV) antiviral prophylaxis have dramatically improved graft and patient survival for patients undergoing liver transplantation for hepatitis B related end-stage liver disease. In particular, the availability of hepatitis B immune globulin (HBIg) in combination with nucleos(t)ide analogues such as lamivudine and adefovir, have transformed outcomes. The availability of newer antivirals such as adefovir, tenofovir and entecavir either as monotherapy or in combination offer an increasing number of antiviral options. Despite these advances, significant challenges remain. Factors that affect the efficacy of anti-viral therapy include detectable HBV viraemia at the time of transplant and emergence of HBV mutants (especially in patients with prior exposure to lamivudine). HBV prophylaxis protocols are expensive especially with use of high-dose HBIg and newer nucleos(t)ide analogues. This review summarizes current HBV prophylaxis protocols and management of recurrent disease post-transplantation. There is an increasing need for individualization of therapy based on prior drug exposures, level of HBV DNA at time of transplantation and type of prophylaxis used.

Bonacini M. · Department of Medicine, University of California at San Francisco, School of Medicine, USA. · J Acquir Immune Defic Syndr. · Pubmed #17704691 No free full text.

Abstract: HIV coinfection is associated with faster progression of liver disease resulting from hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Thus, liver complications have become a major cause of illness and death in coinfected patients. Controlling HIV through highly active antiretroviral therapy may slow disease progression to nearly the rate of HIV-negative persons. Several antiretroviral regimens have been associated with drug-induced liver injury, however, which is more common in patients coinfected with hepatitis B or C. After development of cirrhosis and decompensation, survival is shorter in coinfected patients. Diagnosis and management of cirrhosis should be the same for coinfected and monoinfected HBV/HCV patients. The main complications of cirrhosis are ascites, spontaneous bacterial peritonitis, bleeding esophageal varices, hepatic encephalopathy, the hepatorenal syndrome, and hepatocellular carcinoma. Liver transplantation is feasible in patients with HIV infection, and early evaluation for this option is crucial because of the accelerated course of complications in HIV coinfection.

Terrault NA, Jacobson IM. · Division of Gastroenterology, University of California-San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. · Semin Liver Dis. · Pubmed #17701846 No free full text.

Abstract: As our understanding of the natural history of hepatitis B virus (HBV) infection increases, so do the patient circumstances for which anti-HBV therapy is considered. For example, patients with chronic HBV infection that is negative for hepatitis B surface antigen can experience hepatitis flares during or after cytotoxic chemotherapy and thus are potential candidates for anti-HBV therapy. Also, although passive-active immunoprophylaxis is highly effective in preventing the vertical transmission of HBV, high maternal serum HBV DNA concentrations have been associated with the failure of immunoprophylaxis; for this reason, clinicians may consider administering anti-HBV therapy during pregnancy. However, prophylactic anti-HBV therapy can be both complex and controversial. A satellite symposium conducted during the 57th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, Massachusetts, presented approaches to treating HBV infection in patients who are pregnant and in those who are preparing to receive chemotherapy.

Gish RG, Perrillo RP, Jacobson IM. · Division of Hepatology and Complex GI, Physicians Foundation, California Pacific Medical Center, 2340 Clay Street, San Francisco, CA 94115, USA. · Semin Liver Dis. · Pubmed #17701845 No free full text.

Abstract: As of October 2006, 6 medications are approved in the United States for the management of chronic hepatitis B virus (HBV) infection: 2 formulations of interferon and 4 oral nucleos(t)ide analogues. For the treating practitioner, tailoring the pharmaceutical regimen according to patient features and clinical circumstances can be a challenge. First-line therapeutic regimens for the management of HBV infection include monotherapy with a U.S. Food and Drug Administration-approved agent that has potent on-treatment viral response and low rates of resistance; in the future, these regimens may include a combination of more than one nucleos(t)ide analogue or a combination of a nucleos(t)ide analogue and pegylated interferon. The oral nucleos(t)ide analogues are generally better tolerated than interferon; however, they can be expensive when administered for lengthy periods and can also lead to medication resistance. Lamivudine, the first approved nucleoside analogue for the treatment of HBV infection, has a very high resistance profile; in fact, lamivudine exposure increases viral resistance to other commercially available nucleos(t)ide analogues: entecavir, telbivudine, and adefovir. For these reasons, the 2007 American Association for the Study of Liver Diseases (AASLD) guidelines no longer recommend lamivudine as first-line therapy for the management of HBV infection. A satellite symposium conducted during the 57th Annual Meeting of the AASLD in Boston, Massachusetts, presented approaches to customizing the management of chronic HBV infection. The presentation highlighted recent findings suggesting that early, profound, and sustained viral suppression improves the probability of sustained virologic response and reduces the likelihood of nucleos(t)ide resistance.

Terrault NA, Adey DB. · Department of Medicine, Division of Gastroenterology, University of California, San Francisco, San Francisco, California, USA. · Clin J Am Soc Nephrol. · Pubmed #17699464 links to  free full text

Abstract: Liver disease secondary to chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in dialysis patients and kidney transplant recipients. Evaluation of patients with chronic HCV infection is warranted to determine stage of disease and the need for HCV therapy. Although combination therapy with interferon (IFN) plus ribavirin is the standard of care for chronic HCV infection, IFN monotherapy is recommended in dialysis patients because ribavirin is contraindicated in the presence of renal failure. The goals of pretransplantation HCV therapy are to decrease the risk for progression of HCV-associated liver disease, stabilize renal function in patients with HCV-related glomerulopathy, and prevent development of HCV-associated renal disease after transplantation. Posttransplantation HCV therapy is generally not recommended because of concerns regarding risk for precipitating acute rejection; however, antiviral therapy may be indicated to treat HCV-related glomerulopathy or prevent progression of chronic hepatitis C in patients with more advanced stages of fibrosis. When treatment is required, restored renal function allows use of combination therapy with IFN and ribavirin. Limitations of current HCV therapy include lack of tolerability and suboptimal response rates. New antiviral agents that can be used in dialysis patients (e.g., ribavirin alternatives) and in the posttransplantation setting (e.g., IFN alternatives) are needed to improve outcomes in these populations.

Kadayifci A, Merriman RB, Bass NM. · Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143-0538, USA. · Clin Liver Dis. · Pubmed #17544975 No free full text.

Abstract: There is no proven medical treatment of non-alcoholic steatohepatitis (NASH). Most prior therapeutic trials have had methodologic limitations. Insulin sensitizers are the more promising therapeutic candidates among categories that include antioxidants, lipid-lowering agents, and antiobesity drugs. The future will see the evaluation of novel agents and a comprehensive treatment strategy that addresses the risk factors for the metabolic syndrome. This article reviews the current status of medical management options for NASH.

Busch MR. · Blood Systems Research Institute, San Francisco, CA 94118, USA. · Dev Biol (Basel). · Pubmed #17486883 No free full text.

This publication has no abstract.

Maher JJ. · Rice Liver Center Laboratory, San Francisco General Hospital, 1001 Potrero Avenue, Building 40, Room 4102, San Francisco, CA 94110, USA. · Curr Gastroenterol Rep. · Pubmed #17335676 No free full text.

Abstract: Alcoholic hepatitis is a disease with a wide range of severity. Patients with severe disease have short-term mortality rates above 35%. In these high-risk patients, pharmacologic therapy is an important adjunct to supportive medical care and has been proved to improve survival. Given the benefit of drug treatment, it is important to identify patients at risk of early mortality from alcoholic hepatitis. A number of validated scoring systems are useful for this purpose, including the Maddrey Discriminant Function, the Model of End-Stage Liver Disease score, and the Glasgow Alcoholic Hepatitis score. Patients judged by one or more of these criteria to have severe alcoholic hepatitis should be treated with corticosteroids or pentoxifylline, provided they have no contraindications for this treatment. Adequate nutrition is also critical and should be provided by tube feeding if necessary. A prompt decline in serum bilirubin indicates a favorable response to therapy. Patients who do not exhibit a reduction in serum bilirubin within 1 week are considered nonresponders and have a 6-month mortality rate of 50% or higher.

Gish RG. · Department of Medicine, Division of Hepatology and Complex GI, Physicians Foundation, California Pacific Medical Center, 2340 Clay Street, Room 223, San Francisco, CA 94115, USA. · Curr Gastroenterol Rep. · Pubmed #17335673 No free full text.

Abstract: The ultimate goal in managing patients with chronic hepatitis B (CHB) is to improve long-term outcomes by decreasing deaths and liver transplantation procedures due to hepatitis B virus (HBV)-related cirrhosis and hepatocellular carcinoma. Active intervention and vaccination of individuals susceptible to HBV infection are key steps to decrease the risk of this global public health problem. Large studies have demonstrated that long-term outcomes of CHB are tied to serum levels of HBV DNA. New oral treatments, characterized by potent antiviral effects, good tolerability, improved histology, stable seroconversion, and minimal resistance, are available. Long-term data with oral medications have shown decreased rates of liver cancer development, liver disease reversal, and progression to liver failure. Pegylated interferon trials have demonstrated modest rates of hepatitis B e antigen seroconversion and improved histology after treatment. This paper describes ways to improve outcomes of CHB using vaccines, interferon, lamivudine, adefovir, and newer agents.

Gish RG, Gadano AC. · Division of Hepatology and Complex GI, Physician Foundation, California Pacific Medical Center, San Francisco, CA 94115, USA. · J Viral Hepat. · Pubmed #17109678 No free full text.

Abstract: Hepatitis B virus (HBV) remains a serious health threat in many parts of the world. Although its prevalence is lower in the Americas than in Asia, Africa and the Middle East, it is responsible for significant morbidity and mortality in North, Central and South America. There is a nonuniform pattern of distribution throughout this region, with HBV prevalence related to geographical, social and cultural factors that predispose certain individuals to infection. This report details the incidence, modes of viral transmission of hepatitis B in the Americas and clinical course of disease in different regions of the Americas. Additionally, the implications for management focusing on issues predominant in high-risk populations are presented.

Gish RG, McCashland T. · Department of Transplantation and Medicine, California Pacific Medical Center, San Francisco, CA, USA. · Liver Transpl. · Pubmed #17051551 links to  free full text

Abstract: KEY CONCEPTS: 1. The use of low-dose immunosuppressive therapy along with pre- and posttransplantation nucleos(t)ide therapy and posttransplantation hepatitis B immunoglobulin (HBIG) has yielded marked improvements in survival. 2. Lamivudine (Epivir-HBV), adefovir (Hepsera), entecavir (Baraclude), tenofovir (Viread), emtricitabine (Emtriva), and the combination drugs tenofovir + emtricitabine (Truvada) and abacavir + lamivudine (Epzicom) are effective nucleos(t)ide antiviral agents that, in some cases, may help reverse liver disease sufficiently to avoid transplant. 3. In posttransplantation patients, virus suppression with some combination of HBIG and the nucleos(t)ide agents may prevent graft loss and death or the need for a second transplant. 4. In both the pre- and posttransplantation setting, the goal of hepatitis B virus management is complete virus suppression. 5. The use of low-dose intramuscular HBIG is evolving, with studies showing that dosing and cost can be reduced by 50-300% with a customized approach. 6. Elimination of HBIG from the treatment paradigm is currently under evaluation and may be possible with the use of newer medications that have no or low resistance rates. 7. Although there is growing evidence that some types of combination therapy may decrease the chance that drug resistance will develop and increase the likelihood of long-term success in preventing graft loss and death, additional research will be required to determine which combinations will work well in the long term, and which will not.